Effect of H2-receptor antagonists, cimetidine and ranitidine on reproductive functions in male mice

Na+,K(+)-ATPase and Ca(2+)-ATPase in testis were inhibited with an oral administration of cimetidine and ranitidine. Cimetidine at dose level of 100 and 30 mg while ranitidine at 70 and 10 mg per kg body wt inhibited the enzyme activities, 24 hr after single administration or daily administration for 15-days. Mg(2+)-ATPase activity was increased with cimetidine while ranitidine inhibited the enzyme. Michaelis-Menten kinetic characteristics revealed mixed type of inhibition for Na+,K(+)-ATPase with cimetidine, whereas it was noncompetitive for Ca(2+)-ATPase with cimetidine as well as ranitidine administration. Inhibition of Na+,K(+)-ATPase with ranitidine was also of noncompetitive type. Mg(2+)-ATPase behaved differently with administration of ranitidine at both the time points used i.e. noncompetitive type of inhibition after 24 hr and mixed type after 15-days. Histologically, signs of degeneration of testicular elements appeared after administration of cimetidine with a significant decrease in tubular diameter and germinal epithelial cell height. Ranitidine administration did not produce any change in the seminiferous tubules of testis. Scanning electron microscopy of spermatozoa from cimetidine-treated mice exhibited distinct departure from the normal morphology such as, (i) breaks at various places along distal portion of the tail, (ii) roughening, wrinkling and disorganization of plasma membrane of the head region, (iii) decapitation of the head and (iv) changes in shape of cytoplasmic droplet. Ranitidine administration showed normal morphology of the spermatozoa.